Fluorescent calcium alginate/chitosan microparticles, prepared using a spray-drying techniquefollowed by crosslinking reactions with calcium ions and chitosan, were assayed in-vivo for polymyxinB (PMB) oral toxicity, uptake by Peyer’s patches and PMB oral absorption. A single PMB dose(300 mg kg−1), loaded in microparticles or dissolved in water, was administered to rats by oral gavageunder fasted and fed conditions. By monitoring incidence of mortality, animal behaviour, clinicalsigns and abnormality in several organs, PMB in water solution was found lethal at a dose lowerthan the LD50 (790 mg kg−1) in the fasted state and toxic for the gastrointestinal tract in the fedstate. However, no signs of acute toxicity at the level of the gastrointestinal tract were observedwhen animals were administered PMB loaded in microparticles under fasted and fed conditions.A lower PMB dose (125 mg kg−1), loaded in microparticles or dissolved in water, was given to rats ina fed state to determine PMB levels in Peyer’s patches, urine and serum as well as to detect theloaded microparticles inside Peyer’s patches for three days after dosing. Abnormalities wereobserved at gut level only when PMB was dosed in a water solution. Detectable antibiotic levels inPeyer’s patches and urine as well as more constant PMB serum concentrations were provided by dosingPMB loaded in microparticles. Therefore, the use of alginate/chitosan microparticles to targetthe lymphatic system could improve safety when administering PMB orally.
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|Data di pubblicazione:||2008|
|Titolo:||Toxicity and gut associated lymphoid tissue translocation of polymyxin B orally administered by alginate/chitosan microparticles in rats.|
|Autori:||COPPI G; M. BONDI; COPPI A; ROSSI T; SERGI S; IANNUCCELLI V|
|Digital Object Identifier (DOI):||10.1211/jpp.60.1.0003|
|Appare nelle tipologie:||Articolo su rivista|
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